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The solution to the growing problem of resistance to antibiotics could be lurking somewhere in the depths of the Arctic Ocean.
The possibility that the cold waters of the far north could help resolve one of the biggest problems in modern medicine has been raised by a recent study analysing bacterial samples from the region.
The overuse of antibiotics in recent years means they're becoming less effective, with experts frantically looking for a solution.
But scientists are considering the possibility that the key could be to find new antibiotics whereby the bacteria they are intended to fight are merely inhibited in their harmful actions, rather than killed, thereby reducing the evolutionary necessity to mutate.
Given antimicrobial resistance – when bacteria are able to shake off the effects of antibiotics – claims the lives of about 1.2 million people a year, the findings could be seismic.
Dr Yannik Schneider, researcher at The Arctic University of Norway (UiT) in Tromso and one of the authors of the new study, which has just been published in Frontiers in Microbiology, described the ocean as "underexplored" as he explained why the search for new antibiotics has shifted to the seas.
During a 2020 expedition off Svalbard, an archipelago hundreds of miles north of Norway, researchers found that compounds in types of bacteria called actinobacteria collected from the Arctic Ocean appeared to be able to combat some harmful forms of E. coli.
Actinobacteria from the soil are the source of seven out of 10 current antibiotics, so those in the oceans may too yield useful substances that inhibit the effects of harmful bacteria.
Deep research
According to Dr Schneider, compared to actinobacteria in the soil, those in the sea may be the source of substances with stronger antibiotic effects.
Understanding why this may be the case relates to the purpose for which bacteria produce the compounds we use as antibiotics.
Typically, bacteria create these substances because they help them compete against other microorganisms in their environment.
However, any released into the oceans are likely to become heavily diluted, so scientists believe ocean-based actinobacteria could produce stronger substances out of necessity, to survive.
"The argument is that in the ocean, compounds need to be more active, more potent, in order to have the same effect on other organisms," Dr Schneider said.
"In the soil you have more or less a solid environment, granular or fibrous. In the ocean, you have enormous dilution."
A key part of the research involved demonstrating how advanced methods could be used to simultaneously screen hundreds of compounds from the actinobacteria for their ability to impair the action of enteropathogenic E. coli (EPEC). The EPEC strain analysed can cause fatal diarrhoea in young children.
One of the compounds discovered, T091-5, is seen as particularly promising because it has an antivirulence effect (meaning it impairs the E. coli's ability to cause disease) but does not have an antibacterial effect (so it does not inhibit the E. coli's growth).
This is important because should the substance from T091-5 ever be used as an antibiotic, resistance to it would be less likely to develop.
"If we target pathogenicity, we have less evolutionary pressure to develop resistance. It’s like de-arming a soldier," Dr Schneider said.
More work to do
The corresponding author of the new study, Paivi Tammela, professor of pharmaceutical biology at the University of Helsinki in Finland, cautioned that the results released so far were "very early findings" despite the initial encouragement.
"The compounds will need to be studied much more before we know whether they are good candidates for new antibiotics," she said.
The researchers in Norway, led by Prof Jeanette Anderson of UiT, are now reculturing the most interesting actinobacteria to gain larger quantities.
"[This] would allow, first of all, detailed analytical studies to characterise the compound structure, but also additional biological studies to further investigate their suitability as antibiotics," Prof Tammela said.
A constant battle
Resistant strains of bacteria are increasingly emerging to antibiotics, putting many of the advances of modern medicine at risk.
Routine surgical procedures could become far more dangerous if effective antibiotics are not available to treat infections that appear afterwards.
"It's a huge concern," said Dr Bharat Pankhania, a senior clinical lecturer at the University of Exeter Medical School.
"It can set back medical management of many standard procedures – surgical [operations], hip joints, knee joints, bowel surgery. All these things could be put into jeopardy.
"Without antibiotics, we're taking a huge step backwards in being able to manage things we've taken for granted."
While new antibiotics are one way of trying to solve the problem – albeit temporarily, as resistance is likely to develop over time – Dr Pankhania said better "antibiotic stewardship" was needed, meaning that antibiotics are not given out so readily, as is often the case.
It is also preferable if narrow-spectrum antibiotics, which target a small range of bacteria, are used instead of broad-spectrum antibiotics.
Prof Lars Bjerrum, who researches issues related to the use of antibiotics at the University of Copenhagen, said part of the problem was that antibiotic resistance was a major issue in intensive-care units, but that antibiotics are typically given out by GPs in primary care settings.
"In primary care units you don't see that many patients with severe disease," he said. "Many GPs do not feel it's their business. They give antibiotics and the resistance is created. You select for resistance in primary care and ... in secondary care you have the patients with resistant strains."
One solution that has proved effective at cutting antibiotic use is giving a backup or delayed prescription, in which a prescription is given on the understanding that it will be used only if the condition does not resolve spontaneously.
Meanwhile, the researchers in Norway undertook another research expedition, this time off the coast of the mainland.
"In April we went on a smaller cruise along the Norwegian coast," Dr Schneider said, adding that work was taking place to analyse the material collected.
